Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038362 (stomatitis)
 8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The NS protein of vesicular stomatitis virus is the only phosphorylated nucleocapsid protein. The amount of NS phosphorylation appears to regulate the activity of the protein in the transcription of the virus genome. Several methods have been used to separate NS subspecies containing different amounts of phosphate, but the relationships among the subspecies separated by different workers have been unclear. We report that the isoelectric points of NS molecules were abnormally acidic in some commercial ampholytes, but favorable ampholytes resolved multiple phosphorylated NS subspecies with isoelectric points ranging from pH 6.8 to 7.2. The most highly phosphorylated NS molecules had more acidic isoelectric points, and they exhibited greater electrophoretic mobilities in two previously employed electrophoretic systems.
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PMID:NS phosphoprotein of vesicular stomatitis virus: subspecies separated by electrophoresis and isoelectric focusing. 628 55

We have studied the denaturation and renaturation of the purified glycoprotein (G) of vesicular stomatitis virus by using intrinsic fluorescence spectroscopy and an aggregation assay. Our studies were carried out with G containing two complex oligosaccharide chains, with the asialo form of the protein, and for some experiments with G containing altered oligosaccharide structures. Fluorescence quenching using acrylamide showed no differences between the native and denatured states of G due to sialic acid content. Denaturation by guanidinium chloride (GdmCl) at 25 degrees C was reversible for the major transition region. The data analyzed by a two-state denaturation model gave a free energy of unfolding in the absence of denaturant of approximately 1.4 kcal/mol. For renaturation, two types of dialysis protocols were employed. The first (direct dialysis) involved dialysis against standard buffer [140 mM NaCl, 10 mM sodium phosphate, 1 mM disodium ethylenediaminetetraacetate, and 0.2% (w/v) poly(oxyethylene) 10-tridecyl ether, pH 7.4]. Recovery of the native emission maximum did not occur for any of the G proteins by using this procedure. The second (annealing dialysis) involved slow removal of GdmCl against decreasing concentrations of GdmCl in standard buffer over a period of 2-3 days. Only in this case was recovery of the native emission maximum and fluorescence intensity obtained. For those G proteins in which the oligosaccharide chains were decreased in size, this protocol led to extensive aggregation.
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PMID:Physical properties of the glycoprotein of vesicular stomatitis virus measured by intrinsic fluorescence and aggregation. 628 77

Whole saliva samples and lip biopsies were collected from 12 allogeneic bone marrow transplant recipients who developed extensive chronic graft-versus-host disease (GVHD) and from 10 healthy allogeneic and syngeneic recipients without GVHD. Six of ten biopsies from patients with chronic GVHD had lichenoid stomatitis or sialadenitis, or both, with sialodochitis. Seven of nine biopsies from patients free of chronic GVHD were entirely normal, and two had either mild glandular or mucosal changes. Salivary gland involvement in chronic GVHD was associated with decreased or absent levels of salivary IgA and inorganic phosphate, decreased salivary flow rates, and increased concentrations of salivary sodium, albumin, and IgG. The most striking abnormalities were found in patients with histologic evidence of sialadenitis. In contrast, marrow transplant recipients without chronic GVHD had normal salivary immunoglobulin and electrolyte levels. Secretory IgA deficiency may contribute to the frequent sinobronchial infections observed in patients with chronic GVHD.
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PMID:Disordered salivary immunoglobulin secretion and sodium transport in human chronic graft-versus-host disease. 634 24

In this clinical trial of men with advanced prostatic cancer no longer responsive to hormone therapy 189 were randomized to receive estramustine phosphate, methotrexate or cis-platinum. Response evaluations were done in 158 cases. Objective response rates (complete, partial or stabilization of disease) were 34 per cent for estramustine phosphate, 36 per cent for cis-platinum and 41 per cent for methotrexate. Subjective parameters indicated a substantial advantage for pain improvement with methotrexate or cis-platinum over estramustine phosphate. Probabilities of continued response indicated some advantage for methotrexate and median response durations at this time were twice as long for methotrexate (32 weeks) as for cis-platinum (16 weeks), with estramustine phosphate intermediate (23 weeks). Survival rates for the original treatment randomization groups were not different at this time. Side effects of estramustine phosphate consisted primarily of nausea and vomiting and/or anorexia but to a lesser extent than with cis-platinum. These effects were somewhat less for methotrexate, for which the major side effects were stomatitis and leukopenia, as well as hepatic toxicity reflected by elevated serum glutamic oxaloacetic transaminase levels. Other side effects of cis-platinum were less than for methotrexate (no stomatitis), except for signs of renal toxicity (elevations in blood urea nitrogen and serum creatinine), which were greater. Methotrexate had a relatively high level of activity against metastatic, progressive, hormone nonresponsive prostatic cancer, with side effects that were substantial but manageable.
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PMID:Comparison of estramustine phosphate, methotrexate and cis-platinum in patients with advanced, hormone refractory prostate cancer. 634 29

A Phase I trial of tricyclic nucleoside phosphate (1,4,5,6,8-pentaazaacenaphthylene-3-amino-1, 5-dihydro-5-methyl-1-beta-D-ribofuranosyl 5'-phosphate ester; NSC 280594) was conducted using a 5-day continuous infusion schedule. Thirty-seven patients with advanced cancer were entered on the study, of whom 33 patients were evaluable for response and toxicity. Dose levels ranged from 10 mg/sq m/day X 5 days to 40 mg/sq m/day X 5 days. Initially, courses were repeated every 3 to 4 weeks. As cumulative toxicity became manifested, the interval between courses was changed to every 6 weeks. Major toxicities included hyperglycemia, hepatotoxicity, and thrombocytopenia. Patients with a prior history of diabetes mellitus, extensive radiation therapy, or significant liver metastases were prone to severe toxicity. Other toxicities noted were nausea and vomiting, abdominal discomfort, anemia, and reduction in serum calcium, phosphorus, and albumin levels. Rare side effects included hypertriglyceridemia, hyperamylasemia, diarrhea, and stomatitis. Antitumor activity observed include improvement in s.c. metastases in a patient with papillary thyroid carcinoma, stabilization of disease in a patient with mesothelioma, and mixed responses in three patients (colon cancer, sarcoma, and tonsillar squamous cell cancer). Recommended schedule for Phase II studies is 20 mg/sq m/day for 5 days every 6 weeks.
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PMID:Phase I study of tricyclic nucleoside phosphate using a five-day continuous infusion schedule. 674 83

Tetranitromethane, a protein nitrating agent, was tested for its ability to disinfect surfaces from viruses. Different surfaces on commercially available pocket calculators were pretreated with either the Indiana strain of vesicular stomatitis virus or the Herts' strain of Newcastle disease virus. The calculators surfaces were then sprayed with either tetranitromethane or control solutions. The calculators were incubated for 30 min at ambient temperature, and then the surfaces were wiped with sterile swabs. The swabs were placed into test tubes containing phosphate-buffered saline. Samples of the phosphate-buffered saline were then titered on appropriate cell lines by plaque assay. The results indicated that the amount of vesicular stomatitis virus and Newcastle disease virus recovered from the tetranitromethane-treated surfaces was dramatically decreased compared to the amount of virus recovered from control-treated surfaces. These data suggest that tetranitromethane may be useful to disinfect surfaces from both enveloped and non-enveloped RNA viruses.
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PMID:Tetranitromethane as a surface antiviral disinfectant. 771 Feb 74

Casein kinase-II (CK-II) is a widely distributed protein kinase, which plays numerous roles in the regulation of transcription through modification of transacting transcription factors. Phosphorylation of vesicular stomatitis virus (VSV) P protein by CK-II was found to be both necessary and sufficient for transcriptional activation. Upon treatment of P by CK-II, activity was acquired faster (t1/2 = 3.7 min) than were total phosphates (t1/2 = 7.4 min). Stoichiometry was 2 mol phosphate/mol P, indicating activation by phosphorylation at either one or both of two independent sites. The sites were identified by substituting aspartate (D) residues at either S60 or T62, producing proteins that were partly active without phosphorylation, but were fully active at higher concentrations; CK-II added only a single phosphate group to each of these, and conferred full activity. P protein doubly substituted with D at S60 and T62 was fully active without phosphorylation, and was not a substrate for CK-II. Active P protein, whether CK-II treated or doubly substituted, was shown by gel filtration and crosslinking to exist as a discretely multimeric, probably tetrameric, structure. The singly substituted mutants were partly multimeric, becoming fully so after CK-II treatment. Phosphorylation by CK-II thus mediates the self-association of P into the multimeric, transcriptionally active form.
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PMID:Multimerization and transcriptional activation of the phosphoprotein (P) of vesicular stomatitis virus by casein kinase-II. 772 Jul 14

Fluorescence-activated cell sorting was used to isolate 19 independent, temperature-sensitive, low density lipoprotein (LDL) receptor-deficient Chinese hamster ovary cell mutants that define three recessive complementation groups, ldlE, ldlF, ldlG. LDL receptor activity, essentially normal at the permissive temperature (34 degrees C), was virtually abolished in the mutants after incubation for 8-12 h at the nonpermissive temperature (39-40.5 degrees C). The mutants died after incubation for > 24 h at 39.5 degrees C. These mutants exhibited two striking and unexpected abnormalities that suggest that they define three genes important for general vesicular membrane traffic. First, LDL receptors were degraded abnormally rapidly at the nonpermissive temperature (chloroquine inhibited this degradation in ldlE and ldlG, but not in ldlF). In ldlE cells, the rapid degradation did not require efficient receptor clustering into coated pits and was not observed for all cell surface proteins. This selective degradation may be due to endocytic missorting. Second, the mutants exhibited temperature-sensitive defects in the posttranslational processing and intracellular transport of many membrane-associated and secreted proteins, including the LDL, mannose 6-phosphate/insulin-like growth factor II, and scavenger receptors, the vesicular stomatitis virus G protein and decay accelerating factor. Although the initial synthesis, folding, and processing of precursor forms of these proteins in the endoplasmic reticulum were apparently normal at the nonpermissive temperature, there was either a delay or a block in oligosaccharide processing associated with endoplasmic reticulum to medial Golgi transport at the nonpermissive temperature. This was accompanied by a dramatic inhibition of total soluble protein secretion. The posttranslational processing defects, the instability of cell surface LDL receptors, and the defective protein secretion exhibited by these mutants suggest that the ldlE-G gene products regulate or participate in reactions that are vital for a variety of secretory and endocytic membrane transport processes. This suggestion is strongly supported by our recent observation that a cDNA encoding a component of the coatomer, epsilon-COP, corrects the mutant phenotypes of ldlF cells (Guo, Q., Vasile, E., and Krieger, M. (1994) J. Cell Biol. 125, 1213-1224). Thus, these mutant cells should prove useful for further genetic and biochemical analysis of the mechanisms underlying intracellular membrane traffic.
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PMID:Isolation of three classes of conditional lethal Chinese hamster ovary cell mutants with temperature-dependent defects in low density lipoprotein receptor stability and intracellular membrane transport. 806 14

As a subunit of both the P-L polymerase complex and the P-N assembly complex, the vesicular stomatitis virus (VSV) P protein plays a pivotal role in transcription and replication of the viral genome. Constitutive phosphorylation of this protein is currently thought to be essential for formation of the P-L complex. We recently identified the three relevant phosphate acceptor sites in the VSV Indiana serotype P protein (R. L. Jackson, D. Spadafora, and J. Perrault, Virology 214:189-197, 1995). We now report the effects of substituting Ala at these acceptor sites on transcription reconstitution in vitro and replication of defective interfering virus (DI) templates in vivo. The singly substituted S60A, T62A, and S64A mutants and the doubly substituted S60A/T62A and T62A/S64A mutants, all of which retain some constitutive phosphorylation, were nearly as active as the wild type in both assays. Surprisingly, the nonphosphorylated S60A/S64A protein was also active in transcription (> or = 28%)) and replication (> or = 50%) under optimal conditions. However, this mutant was much less active in in vitro transcription (< or = 5% of wild type) at low P concentrations (<27 nM). In addition, S60A/S64A required higher concentrations of L protein than did the wild type for optimal DI replication in vivo. DI replication efficiency and intracellular accumulation of L, P, and N proteins in the transfected system were very similar to those in VSV-infected cells. We conclude that P protein constitutive phosphorylation is not essential for VSV RNA synthesis per se but likely plays an important role in vivo in facilitating P multimerization and possibly P-L complex formation.
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PMID:Constitutive phosphorylation of the vesicular stomatitis virus P protein modulates polymerase complex formation but is not essential for transcription or replication. 867 80

Etoposide phosphate (EP) is a water-soluble derivative of etoposide (VP-16), a semisynthetic podophyllotoxin which is useful in the treatment of a wide variety of hematological malignancies and solid tumors. Because etoposide is poorly water soluble, it must be dissolved in a variety of organic solvents and given in relatively large volumes of saline. EP is rapidly converted to the parent drug in vivo and has been shown to be active in animal studies. We performed a phase I pharmacokinetic study in 27 patients. Three patients each received an etoposide-equivalent dose of 50 or 75 mg/m2 each day by i.v. bolus (5 min) daily for 5 days and 21 patients received a dose equivalent to 100 mg/m2 of etoposide each day for 5 days. Non-compartmental pharmacokinetic data were obtained for 22 of the patients. As with previous studies, EP behaves as a prodrug of etoposide. The Cmax (25.3-42.5 micrograms/ml) increased linearly, while AUCinf (75.8-156 h micrograms/ml) of etoposide increased proportionately with dose (50-100 mg/m2 of etoposide equivalents). Time to achieve Cmax corresponded to the end of the 5 min injection, indicating a rapid formation of etoposide from EP. Mean etoposide phosphate/etoposide Cmax and AUCinf ratios were 0.08 or less and 0.003, respectively, indicating that the major circulating moiety in plasma was etoposide. Parameters such as MRT, T1/2, CL/F, CLR, VSS/F and %UR were dose independent. The toxicities of EP were virtually identical to those seen with etoposide, with dose-related myelosuppression, alopecia and stomatitis. Severe neutropenia was the dose-limiting toxicity. No significant problems with hypotension or allergic reactions were observed. No problems, difficulties or complications were observed as a result of bolus (5 min) administration. On the basis of phase I toxicity data, we recommend an etoposide equivalent starting dose of 100 mg/m2/day for 5 days in previously untreated patients who have an excellent performance status. In patients who have had one or more prior chemotherapy regimens, extensive prior radiation therapy or moderately impaired performance status, we recommend an etoposide phosphate starting dose of 75 mg/m2/day for 5 days with courses repeated at 3 week intervals.
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PMID:Phase I and pharmacokinetic study of etoposide phosphate. 884 73


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